Fasting before living-kidney donation: effect on donor well-being and postoperative recovery: study protocol of a multicenter randomized controlled trial.

BACKGROUND: One of the main effectors on the quality of life of living-kidney donors is postoperative fatigue. Caloric restriction (CR) and short-term fasting (STF) are associated with improved fitness and increased resistance to acute stress. CR/STF increases the expression of cytoprotective genes, increases immunomodulation via increased anti-inflammatory cytokine production, and decreases the expression of pro-inflammatory markers. As such, nutritional preconditioning by CR or STF represents a non-invasive and cost-effective method that could mitigate the effects of acute surgery-induced stress and postoperative fatigue. To investigate whether preoperative STF contributes to a reduction in fatigue after living-kidney donation, a randomized clinical trial is indicated. METHODS: We aim to determine whether 2.5 days of fasting reduces postoperative fatigue score in subjects undergoing living-kidney donation. In this randomized study, the intervention group will follow a preoperative fasting regime for 2.5 days with a low-dose laxative, while the control group will receive standard care. The main study endpoint is postoperative fatigue, 4 weeks after living-kidney donation. Secondary endpoints include the effect of preoperative fasting on postoperative hospital admission time, the feasibility of STF, and the postoperative recovery of donor and recipient kidney function. This study will provide us with knowledge of the feasibility of STF and confirm its effect on postoperative recovery. DISCUSSION: Our study will provide clinically relevant information on the merits of caloric restriction for living-kidney donors and recipients. We expect to reduce the postoperative fatigue in living-kidney donors and improve the postoperative recovery of living-kidney recipients. It will provide evidence on the clinical merits and potential caveats of preoperative dietary interventions. TRIAL REGISTRATION: Netherlands Trial Register NL9262 . EudraCT 2020-005445-16 . MEC Erasmus MC MEC-2020-0778. CCMO NL74623.078.21.

Circulating endothelial cells transiently increase in peripheral blood after kidney transplantation.

The diagnosis of kidney allograft rejection is based on late histological and clinical markers. Early, specific and minimally-invasive biomarkers may improve rejection diagnosis. Endothelial cells (EC) are one of the earliest targets in kidney transplant rejection. We investigated whether circulating EC (cEC) could serve as an earlier and less invasive biomarker for allograft rejection. Blood was collected from a cohort of 51 kidney transplant recipients before and at multiple timepoints after transplantation, including during a for cause biopsy. The number and phenotype of EC was assessed by flow-cytometric analysis. Unbiased selection of EC was done using principal component (PCA) analysis. Paired analysis revealed a transient cEC increase of 2.1-fold on the third day post-transplant, recovering to preoperative levels at seventh day post-transplant and onwards. Analysis of HLA subtype demonstrated that cEC mainly originate from the recipient. cEC levels were not associated with allograft rejection, allograft function or other allograft pathologies. However, cEC in patients with allograft rejection and increased levels of cEC showed elevated levels of KIM-1 (kidney injury marker-1). These findings indicate that cEC numbers and phenotype are affected after kidney transplantation but may not improve rejection diagnosis.

Care for the organ transplant recipient on the intensive care unit.

All transplant recipients receive tacrolimus, mycophenolate and glucocorticoids and these drugs have many side-effects and drug-drug interactions. Common complications include surgical complications, infections, rejection and acute kidney injury. Infections as CMV and PJP can be prevented with prophylactic treatment. Given the complexity of organ transplant recipients a multi-disciplinary team of intensivists, surgeons, pharmacists and transplant specialists is essential. After heart transplantation a temporary pacemaker is required until the conduction system recovers. Stiffening of the heart and increased cardiac markers indicate rejection. An endomyocardial biopsy is performed via the right jugular vein, necessitating its preservation. For lung transplant patients, early intervention for aspiration is warranted to prevent chronic rejection. Risk of any infection is high, requiring active surveillance and intensive treatment, mainly of fungal infections. The liver is immunotolerant requiring lower immunosuppression. Transplantation surgery is often accompanied by massive blood loss and coagulopathy. Other complications include portal vein or hepatic artery thrombosis and biliary leakage or stenosis. Kidney transplant recipients have a high risk of cardiovascular disease and posttransplant anemia should be treated liberally. After postmortal transplantation, delayed graft function is common and dialysis is continued. Ureteral anastomosis complications can be diagnosed with ultrasound.

Safety and feasibility of 2 h of normothermic machine perfusion of donor kidneys in the Eurotransplant Senior Program.

BACKGROUND: The 5-year graft survival rate of donor kidneys transplanted in the Eurotransplant Senior Program (ESP) is only 47 per cent. Normothermic machine perfusion (NMP) may be a new preservation technique that improves graft outcome. This pilot study aimed to assess safety and feasibility of this technique within the ESP. METHODS: Recipients were eligible for inclusion if they received a donor kidney within the ESP. Donor kidneys underwent 2 h of oxygenated NMP with a red cell-based solution at 37°C, additional to standard-of-care preservation (non-oxygenated hypothermic machine perfusion). The primary outcome was the safety and feasibility of NMP. As a secondary outcome, graft outcome was investigated and compared with that in a historical group of patients in the ESP and the contralateral kidneys. RESULTS: Eleven patients were included in the NMP group; the function of eight kidneys could be compared with that of the contralateral kidney. Fifty-three patients in the ESP, transplanted consecutively between 2016 and 2018, were included as controls. No adverse events were noted, especially no arterial thrombosis or primary non-function of the transplants. After 120 min of oxygenated NMP, median flow increased from 117 (i.q.r. 80-126) to 215 (170-276) ml/min (P = 0.001). The incidence of immediate function was 64 per cent in the NMP group and 40 per cent in historical controls (P = 0.144). A significant difference in graft outcome was not observed. DISCUSSION: This pilot study showed NMP to be safe and feasible in kidneys transplanted in the ESP. A well powered study is warranted to confirm these results and investigate the potential advantages of NMP on graft outcome.

Living Donor Kidney Transplantation in a Patient With Epidermolysis Bullosa: A Case Report.

Severe recessive dystrophic epidermolysis bullosa is a very rare inherited disease with excessive blisters forming starting at birth. Surgical intervention in this population creates a challenge: preventing formation of new lesions while managing previously scarred tissues. We present a case of a 27-year-old patient with end-stage renal disease caused by rapidly progressive IgA nephropathy. Living donor kidney transplantation was performed under local, spinal and epidural anesthesia. Living kidney transplantation in epidermolysis bullosa patients with end-stage renal disease should not be a contraindication for transplantation and should be considered as a viable and feasible option after careful preparation.

Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review.

Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment, specifically with anti-interleukin 2 receptor antibodies (IL2RAb) and anti-tumor necrosis factor-α antibodies (TNFAb), has gained increasing interest. However, evidence is mostly limited to case reports and the efficacy remains unclear. Here, we describe 5 patients with LTx-associated GVHD from our center and provide the results of our systematic literature review to evaluate the potential therapeutic benefit of IL2RAb/TNFAb treatment. Of the combined population of 155 patients (5 in our center and 150 through systematic search), 24 were given mAb (15.5%)-4 with TNFAb (2.6%) and 17 with IL2RAb (11%) ("mAb group")-and compared with patients who received other treatments (referred to as "no-mAb group"). Two-sided Fisher exact tests revealed a better survival when comparing treatment with mAb versus no-mAb (11/24 vs 27/131; P = .018), TNFAb versus no-mAb (3/4 vs 27/131; P = .034), and IL2RAb versus no-mAb (8/17 vs 27/131; P = .029). This systematic review suggests a beneficial effect of mAb treatment and a promising role for TNFAb and IL2RAb as a first-line strategy to treat LTx-associated acute GVHD.

DCD donor hemodynamics as predictor of outcome after kidney transplantation.

Insufficient hemodynamics during agonal phase-ie, the period between withdrawal of life-sustaining treatment and circulatory arrest-in Maastricht category III circulatory-death donors (DCD) potentially exacerbate ischemia/reperfusion injury. We included 409 Dutch adult recipients of DCD donor kidneys transplanted between 2006 and 2014. Peripheral oxygen saturation (SpO2-with pulse oximetry at the fingertip) and systolic blood pressure (SBP-with arterial catheter) were measured during agonal phase, and were dichotomized into minutes of SpO2 > 60% or SpO2 < 60%, and minutes of SBP > 80 mmHg or SBP < 80 mmHg. Outcome measures were and primary non-function (PNF), delayed graft function (DGF), and three-year graft survival. Primary non-function (PNF) rate was 6.6%, delayed graft function (DGF) rate was 67%, and graft survival at three years was 76%. Longer periods of agonal phase (median 16 min [IQR 11-23]) contributed significantly to an increased risk of DGF (P = .012), but not to PNF (P = .071) and graft failure (P = .528). Multiple logistic regression analysis showed that an increase from 7 to 20 minutes in period of SBP < 80 mmHg was associated with 2.19 times the odds (95% CI 1.08-4.46, P = .030) for DGF. In conclusion, duration of agonal phase is associated with early transplant outcome. SBP < 80 mmHg during agonal phase shows a better discrimination for transplant outcome than SpO2 < 60% does.

Successful Use of Ectopic Pelvic Kidney for Living Related Donation Technical Aspects and Literature Review.

Ectopic pelvic kidneys can provide an additional source of organs for transplantation. They are often excluded from donation in living donation programs mainly due to aberrant vascular and urinary anatomies. We present a donor with an ectopic left kidney, who successfully donated his kidney. The use of ectopic pelvic kidney for living kidney transplantation is a highly demanding surgical procedure but after extensive preoperative investigation in high volume centers with surgical expertise in vascular reconstruction and access surgery, ectopic pelvic kidneys should not be a contraindication for donation and should be considered as a viable option.

Duplicated ureters and renal transplantation: a case-control study and review of the literature.

INTRODUCTION: Complications of the transplant ureter are the most important cause of surgical morbidity after renal transplantation. The presence of ureteral duplication in the renal graft might result in an increased complication rate. We analyzed our data of double-ureter renal transplantations using a case-control study design. Additionally, we performed a review of the literature. METHODS: From January 1995 to April 2012, 12 patients received a donor kidney with a double ureter (0.8%). We created a control group of 24 patients matched in age, sex, donor type, and ureteral stenting. Patient charts and surgical reports were reviewed retrospectively. RESULTS: In 7 patients both ureters were separately anastomosed to the bladder. In 4 patients a common ostium was created. In 1 patient 1 of the 2 ureters was ligated. No postoperative urologic complications occured. In the single-ureter group, the urologic complication rate was 17% (P = .71). Mean creatinine levels after transplantation were comparable between both groups. DISCUSSION: A double-ureter donor kidney is not associated with an increased complication rate after renal transplantation and yields equal outcomes as compared to single-ureter donor kidneys. We conclude that transplantation of a kidney with a duplicated ureter is safe.

Ureteral reconstruction after renal transplantation: clinical outcome and risk factors.

INTRODUCTION: The incidence of urological complications after renal transplantation ranges from 2.5 to 30%. Often surgical revision is necessary. The risk factors for surgical revision and which surgical techniques to apply are not elucidated. This study investigates the outcome and risk factors for surgical revision of the ureterocystostomy. MATERIALS AND METHODS: Between January 1995 and March 2009, 1,157 consecutive kidney transplantations were performed. All patient charts and surgical reports were reviewed. RESULTS: Urological complications occurred in 142 (12.3%) patients. In 60 patients (5.2%) surgical revision was necessary. Of these 60 patients, 43 (71.7%) received neoureterocystostomy, 10 (16.7%) ureteropyelostomy reconstruction and 7 (11.7%) other techniques. Independent risk factors for surgical revision were donor ureteral reconstruction (odds ratio (OR) 48.66, 95% confidence interval (CI) 5.01-472.97), recipient age <18 years (OR 4.85, 95% CI 1.50-15.72) and delayed graft function (OR 2.70, 95% CI 1.36-5.36). Ureteral stenting was a protective factor for surgical revision (OR 0.30, 95% CI 0.12-0.81). The urological complication rates after neoureterocystostomy, ureteropyelostomy reconstruction and other techniques were 16, 0 and 0%, respectively. The overall surgical success rate was 92%. CONCLUSIONS: Ureteral stenting, recipient age, delayed graft function and perioperative ureteral reconstruction are significant factors associated with surgical revision of the ureterocystostomy. Surgical revision of the ureterocystostomy is a successful therapy with a low recurrence rate.

Risk of malignant lymphoma in patients with inflammatory bowel diseases: a Dutch nationwide study.

BACKGROUND: Immune suppressant medications such as thiopurines and anti-tumor necrosis factor agents are important for maintaining disease control in most patients with inflammatory bowel diseases (IBDs); however, their use has been associated with the development of malignant lymphoma. The purpose of this Dutch nationwide study was to estimate the relative risk of malignant lymphoma in IBD patients. METHODS: IBD patients who developed a lymphoma between 1997 and 2004 were identified using the Dutch National Database of PALGA. Data from confirmed cases were collected from individual hospitals, including data on Epstein-Barr virus (EBV). The age-adjusted 8-year incidence of malignant lymphoma in the Netherlands was retrieved from the Central Bureau of Statistics. RESULTS: Forty-two hospitals were visited and 285 matches evaluated in the total cohort of 17,834 IBD patients. Forty-four lymphomas were observed, resulting in a relative risk of 1.27 (95% confidence interval [CI]: 0.92-1.68). Only 19 of 44 patients (43%) were exposed to azathioprine/6-mercaptopurine (AZA/6-MP). Remarkably, 92% of patients (11/12) with EBV-positive lymphoma used AZA/6-MP, in contrast to only 19% patients (4/21) with EBV-negative lymphoma, suggesting a strong relation between EBV-positive lymphoma and thiopurine use. CONCLUSIONS: This nationwide study does not suggest a significant overall increased risk for lymphoma in IBD patients. A distinct correlation between EBV-positive lymphoma and AZA/6-MP use was observed.

Risk factors for delayed graft function after hand-assisted laparoscopic donor nephrectomy.

BACKGROUND: Delayed graft function (DGF) has a negative effect on the results of living-donor kidney transplantation. OBJECTIVE: To investigate potential risk factors for DGF. METHODS: This prospective study included 200 consecutive living donors and their recipients between January 2002 and July 2007. Delayed graft function was defined as need for dialysis within the first postoperative week. RESULTS: Delayed graft function was diagnosed in 12 patients (6%). Intraoperative complications occurred in 10 donors (5%), and postoperative complications in 24 donors (13.5%). One-year kidney graft survival with vs without DGF was 52% and 98%, respectively (P < .002). In donors, 2 univariate risk factors for DGF identified were lower counts per second at peak activity during scintigraphy, and multiple renal veins. In recipients, only 2 or more kidney transplantations and occurrence of an acute rejection episode were important factors. At multivariate analysis, increased risk of DGF was associated with the presence of multiple renal veins (odds ratio, 151.57; 95% confidence interval, 2.53-9093.86) and an acute rejection episode (odds ratio, 78.87; 95% confidence interval, 3.17-1959.62). CONCLUSION: Hand-assisted laparoscopic donor nephrectomy is a safe procedure. The presence of multiple renal veins and occurrence of an acute rejection episode are independent risk factors for DGF.

Laparoscopic donor nephrectomy.

Living donor nephrectomy has been developed and promoted as a method to address the shortfall in kidneys available for transplantation. The classical method to procure a kidney from a living donor is the open donor nephrectomy performed through a flank lumbotomy incision. However, this classical method has negative short- and long-term side effects for the donor. These disincentives are a drawback for possible donors to donate a kidney. Therefore, transplant surgeons were stimulated to develop new and less invasive techniques. In this review several new open and laparoscopic techniques are described. Compared with open donor nephrectomy, laparoscopic donor nephrectomy has shown superior results in terms of postoperative pain, cosmetics, convalescence, and return to normal daily activities. No significant differences exist between the two approaches in terms of complication rates, cost-effectiveness and graft function. Nowadays, laparoscopic donor nephrectomy has become the preferred method for procuring kidney grafts of living donors in many centres.

Aortic aneurysm and orchitis due to Wegener's granulomatosis.

We present a patient with Wegener's granulomatosis (WG) with involvement of the abdominal aorta, testis, peripheral nerve system, and skin. A 51-year-old man presented at our outpatient clinic with lower back pain. He had a history of smoking, hypertension, and an embryonal carcinoma of the left testis, treated 13 years ago with orchidectomy and chemotherapy. One month earlier, he underwent a partial orchidectomy of the right testis due to testicular swelling. Abdominal computed tomography showed a 3.8 cm wide aneurysm of the distal part of the aorta with inflammation. One week later he was admitted to the hospital with numbness of his hands and feet. Physical examination showed signs of peripheral microemboli. Serological laboratory tests revealed elevated antineutrophil cytoplasmic antibody titers with positive reactions against proteinase-3, indicating Wegener's disease. The chest X-ray was normal. Pathological examination of the right testis showed necrotizing vasculitis of a small artery. He was treated with cyclophosphamide and prednisolone. WG with extrapulmonary involvement occurs infrequently, and reports of manifestations of WG in aorta, testis, the peripheral nerve system, and skin are even more uncommon. Small- and medium-vessel vasculitis can precede large-vessel vasculitis or occur in the absence of small-vessel involvement. Therefore, WG should be included in the work-up of large-vessel vasculitis, which can give rise to periaortic inflammation.

[Pneumocystis pneumonia during infliximab treatment for active Crohn's colitis]. / Pneumocystis-pneumonie tijdens behandeling met infliximab voor actieve Crohn-colitis.

A 51-year-old man with Crohn's disease for 22 years presented with a dry cough, dyspnoea, fever and diarrhoea. He had steroid-resistant Crohn's disease. Because of nausea complaints, azathioprine was switched to methotrexate with concomitant infliximab induction therapy. During infliximab therapy, symptoms occurred for which the patient was hospitalised and Pneumocystis pneumonia (PCP) was diagnosed by examination of bronchoalveolar lavage fluid; it was successfully treated with co-trimoxazole and prednisolone. The exacerbation of the Crohn's colitis diminished. This is the first Dutch case history of PCP during combination therapy with prednisolone, methotrexate and infliximab. Infliximab treatment has been associated with an increased risk for infectious complications. For patients with Crohn's disease, one should consider giving PCP prophylaxis for the duration of lymphocytopenia on an individual basis, weighing the adverse effects ofco-trimoxazole against the risk of PCP. A CD4-cell count < 0.2 x 10(9)/l or a lymphocyte count < 0.6 x 10(9)/l may be used as a guide.